DNA Methylation Testing for Thyroid Nodules

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: City of Hope Medical Center

Disqualifiers: Children

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

1450 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method to identify thyroid cancer using DNA methylation (a change in DNA that can affect gene activity) in thyroid nodules. The goal is to develop a more accurate test to distinguish between cancerous and non-cancerous thyroid nodules, potentially helping people avoid unnecessary surgeries. Participants will undergo a needle biopsy (also known as a fine needle aspiration biopsy), where a small tissue sample is taken from their thyroid for analysis. This trial suits those already undergoing a needle biopsy for thyroid nodules and who can make their own medical decisions. As an unphased trial, it offers participants the chance to contribute to innovative research that could lead to more accurate diagnostic methods.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

What prior data suggests that this diagnostic procedure is safe for thyroid nodule testing?

Research has shown that the DNA methylation test is a promising method for detecting thyroid cancer. This test examines changes in DNA within thyroid nodules to determine if a growth is cancerous.

Studies have found the needle biopsy part of the test to be very safe. This procedure uses a thin needle to extract a small tissue sample. Most people experience no serious issues, with only minor problems like slight bleeding or a small risk of infection. These complications are rare, making the needle biopsy a trusted and reliable method for examining thyroid nodules.

Overall, the combination of DNA methylation testing and needle biopsy is well-tolerated by patients. These methods are considered safe, with very few reports of serious side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about DNA methylation testing for thyroid nodules because it offers a new way to improve diagnostic accuracy. Unlike traditional methods that rely solely on imaging or cytology, this approach analyzes tissue samples for specific DNA methylation patterns using the DDMS-2 system. This technique could help differentiate between benign and malignant nodules more precisely, potentially reducing the need for unnecessary surgeries and enhancing patient care.

What evidence suggests that this diagnostic procedure is effective for thyroid nodules?

Research has shown that DNA methylation testing, which participants in this trial may undergo, could aid in diagnosing thyroid nodules. One study found it could distinguish between non-cancerous and cancerous nodules with up to 96% accuracy. Another study reported that this test correctly identified 92% of potentially cancerous nodules, but it was only 52% accurate in ruling out non-cancerous ones. Specifically, the test correctly diagnosed 73% of cancers in patients with unclear thyroid nodules. Meanwhile, needle biopsies, also used in this trial to collect tissue samples, have an accuracy rate of 80% to 90% for diagnosing thyroid nodules. Together, these methods offer promising tools for better diagnosis, potentially reducing unnecessary surgeries. ^{2 3 6 7 8}

Who Is on the Research Team?

John H. Yim

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

This trial is for adults with thyroid nodules who are undergoing needle biopsies. Participants must be able to give informed consent and have the capacity to make decisions about their healthcare. Children are excluded because the biology of their thyroid nodules differs from that of adults.

Inclusion Criteria

I am over 18 years old.

My gender, race, or ethnicity does not limit my participation.

I am mentally capable and scheduled for a thyroid biopsy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Diagnostic

Participants undergo needle biopsy for collection of tissue samples, which are analyzed using DDMS-2

1 week

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after diagnostic procedures

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Diagnostic Procedure
• Needle Biopsy

Trial Overview The study is testing a new diagnostic method using DNA methylation signatures from needle biopsy samples to distinguish between malignant (cancerous) and benign (non-cancerous) thyroid tumors, aiming to reduce unnecessary surgeries.

How Is the Trial Designed?

Group I: Diagnostic (needle biopsy, DDMS-2) Experimental Treatment 3 Interventions

Patients undergo needle biopsy for collection of tissue samples. Tissue samples are analyzed using DDMS-2. Patients' medical records are also reviewed.

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a study of 505 patients undergoing fine needle aspiration biopsy (FNAB) for thyroid nodules, the specimen adequacy ratio was found to be 85.3%, with larger nodules yielding more diagnostic samples (6.00 mL vs. 3.05 mL for non-diagnostic samples).

Predominantly solid nodules had better specimen adequacy (87.8%) compared to predominantly cystic nodules (75.3%), and cystic nodules took longer for definitive cytological diagnosis (376 seconds vs. 294 seconds for solid nodules), suggesting that repeated sampling may be necessary for cystic nodules.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Thyroid fine needle aspiration biopsy: do nodule volume and cystic degeneration ratio affect specimen adequacy and cytological diagnosis time? Cengic, I., Tureli, D., Ozden, F., et al.[2015]

In a study of 474 patients with thyroid nodules ≥4 cm that had benign fine-needle aspiration biopsies, 5.3% were found to be malignant upon surgery, highlighting the potential for false negatives in FNAB results.

Younger patients (under 55 years old) had a significantly higher risk of malignancy (7.7%) compared to older patients (2.0%), indicating that age is an important factor in assessing the risk of malignancy in large thyroid nodules.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is patient age associated with risk of malignancy in a ≥4 cm cytologically benign thyroid nodule? Sutton, W., Canner, JK., Rooper, LM., et al.[2022]

The study analyzed fine needle aspiration biopsies (FNABs) from 117 patients and found that combining BRAF(V600E) mutation detection with DNA methylation markers significantly improved the diagnostic accuracy for papillary thyroid cancer (PTC).

BRAF(V600E) mutations were present in 71.4% of FNABs from patients with PTC, and specific methylation patterns of genes like DAPK1 and RASSF1A further distinguished malignant from benign nodules, enhancing the sensitivity and specificity of the diagnosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of BRAF(V600E) mutation and DNA methylation improves the diagnostics of thyroid fine needle aspiration biopsies. Zhang, B., Liu, S., Zhang, Z., et al.[2021]

Sequential fine-needle aspiration biopsy (FNAB) significantly improves the accuracy, sensitivity, and specificity of diagnosing thyroid nodules, with accuracy increasing by 22.6% and sensitivity by 13.8% compared to single FNABs.

While sequential FNABs are more costly (70% higher per patient), they reduce false positive/negative results by 14.2% and eliminate nondiagnostic results, potentially leading to lower overall healthcare costs by improving treatment selection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single versus sequential fine-needle aspiration biopsy in the management of thyroid nodular disease. Furlan, JC., Bedard, YC., Rosen, IB.[2018]

About 15-30% of thyroid nodules are classified as indeterminate after fine-needle aspiration biopsy (FNAB), and understanding their molecular causes can help reduce unnecessary surgeries.

Current molecular tests, including mutation detection and gene expression analysis, show promise in improving the diagnosis of thyroid cancer in indeterminate cases, but more validation and local data are needed before they can be routinely used.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Can current molecular tests help in the diagnosis of indeterminate thyroid nodule FNAB? Ferraz, C.[2023]

A new diagnostic tool using DNA methylation biomarkers can effectively differentiate between benign and malignant thyroid lesions, achieving up to 94.3% sensitivity and 82.4% specificity in identifying thyroid cancers.

This tool shows promise in preoperative screening, potentially reducing unnecessary surgeries for patients with thyroid nodules, especially in cases with indeterminate cytology, where it demonstrated 100% sensitivity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

DNA Methylation-Based Method to Differentiate Malignant from Benign Thyroid Lesions. Barros-Filho, MC., Dos Reis, MB., Beltrami, CM., et al.[2020]

Molecular testing has become a crucial part of managing thyroid nodules, especially for those with indeterminate biopsy results, as it helps clarify the risk of malignancy and guides treatment decisions.

Advancements in understanding the genetic landscape of thyroid cancers, particularly papillary thyroid carcinoma, have improved the accuracy of molecular tests, allowing for more personalized and effective management strategies for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Update on Molecular Diagnostics in Thyroid Pathology: A Review. Alzumaili, B., Sadow, PM.[2023]

A new molecular diagnostic test for thyroid cancer, based on DNA methylation analysis of 109 thyroid tissues, shows significant differences between benign nodules, adjacent tissues, and cancerous tissues, leading to improved diagnostic accuracy.

In a validation cohort of 65 thyroid nodules, the test demonstrated exceptional performance with 100% sensitivity and 97% specificity, indicating it can accurately identify cancerous nodules while minimizing unnecessary surgeries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identification of Tissue-Specific DNA Methylation Signatures for Thyroid Nodule Diagnostics. Yim, JH., Choi, AH., Li, AX., et al.[2020]

Fine needle biopsy (FNB) is the safest and most effective method for evaluating thyroid nodules, with specific sampling techniques recommended to minimize false negatives, such as taking at least 6 aspirates and ensuring adequate benign cell clusters.

FNB results can be reliable enough to guide surgical decisions, and patients with benign diagnoses should be monitored, with re-biopsy recommended for nodules that do not shrink after one year of treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fine needle biopsy diagnosis of thyroid nodules. Perspective. Hamburger, JI.[2016]

In a study of 66 patients with solitary thyroid nodules diagnosed as follicular neoplasms, intraoperative frozen-section analysis did not significantly improve the diagnosis of malignancy compared to existing clinical and cytological data.

Out of 64 deferred cases, only 15 were found to be malignant upon final pathology, indicating that routine frozen-section analysis may not be beneficial for distinguishing between benign and malignant follicular lesions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Frozen section in a cytological diagnosis of thyroid follicular neoplasm. Alonso, N., Lucas, A., Salinas, I., et al.[2004]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S1567576925004163

Research progress of DNA methylation in the diagnosis ... This panel achieved an impressive area under the curve (AUC) value of up to 96 % in differentiating benign thyroid nodules from PTC, showcasing ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9996242/

Cell-free DNA methylation biomarker for the diagnosis ... We aimed to establish a cfDNA-based DNA methylation marker panel to differentially diagnose papillary thyroid carcinoma (PTC) from benign thyroid nodule (BTN).

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8964406/

Integrative Analysis of DNA Methylation and Gene ... A high sensitivity (92%), but a low specificity (52%) was found in the identification of suspicious nodules. In this study, we analyzed DNA methylation and gene ...

4. withpower.com withpower.com/trial/phase-thyroid-neoplasms-9-2021-3605c

DNA Methylation Testing for Thyroid Nodules This clinical trial evaluates deoxyribonucleic acid (DNA) methylation signatures in diagnosing and managing thyroid nodules. The purpose of this research is ...

5. academic.oup.com academic.oup.com/jcem/article/91/1/98/2843286

A Novel Diagnostic Tool for Thyroid Cancer - Oxford Academic In a subset of patients with cytologically indeterminate thyroid nodules, serum DNA methylation testing could correctly diagnose eight of 11 (73%) cancers and ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03676647

NCT03676647 | Diagnostic DNA Methylation Signature in ... This trial studies how well the diagnostic deoxyribonucleic acid (DNA) methylation signature works in detecting thyroid cancer in patients with thyroid nodules.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11238273/

Microarray-Based DNA Methylation Profiling - PubMed Central Microarray-based methylation profiling has emerged as a valuable tool for refining diagnoses and revealing novel tumor subtypes, particularly in central nervous ...

8. erc.bioscientifica.com erc.bioscientifica.com/view/journals/erc/26/7/ERC-19-0093.xml

DNA methylation in thyroid cancer in All these studies showed that thyroid cancer is not an exception and exhibits DNA methylation alterations. However, different pan-cancer ...